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Int J Pharm. 2017 Jan 10;516(1-2):61-70. doi: 10.1016/j.ijpharm.2016.11.012. Epub 2016 Nov 5.

Folic acid-decorated and PEGylated PLGA nanoparticles for improving the antitumour activity of 5-fluorouracil.

Author information

1
Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Granada, Spain; Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, University of Damascus, Syria.
2
Department of Applied Physics, Faculty of Sciences, University of Granada, Spain.
3
Institute of Biopathology and Regenerative Medicine (IBIMER), University of Granada, Spain; Biosanitary Institute of Granada (ibs.GRANADA), Andalusian Health Service (SAS), University of Granada, Spain.
4
Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Granada, Spain; Institute of Biopathology and Regenerative Medicine (IBIMER), University of Granada, Spain; Biosanitary Institute of Granada (ibs.GRANADA), Andalusian Health Service (SAS), University of Granada, Spain. Electronic address: jlarias@ugr.es.

Abstract

5-Fluorouracil (5-FU) is a broad spectrum cytotoxic agent being used in chemotherapy of malignancies. However, 5-FU shows a number of limitations like short half-life, non-selective biodistribution, and the development of drug resistances by tumour cells. It was investigated the potential use of folic acid-decorated and PEGylated poly(D,L-lactide-co-glycolide) nanoparticles (FOL-PEG-PLGA NPs) for the targeted delivery of 5-FU to colon and breast cancers. PEG-PLGA and FOL-PEG-PLGA conjugates were synthesized and characterized. NPs of PLGA, PEG-PLGA, and FOL-PEG-PLGA were prepared by nanoprecipitation under optimal formulation conditions. They were found to be haemocompatible, and exhibited negligible cytotoxicity in normal (CCD-18 and MCF-10A) and tumour (HT-29 and MCF-7) human cell lines. 5-FU loading capabilities were also defined, and the NPs exhibited an initial burst drug release followed by a sustained 5-FU release. In vitro cytotoxicity studies in folate-overexpressed HT-29 colon cancer cells and MCF-7 breast cancer cells demonstrated that the half maximal inhibitory concentration (IC50) of 5-FU-loaded FOL-PEG-PLGA NPs was approximately 4-fold less than that of the 5-FU-loaded PLGA NPs (p<0.05). Consequently, FOL-PEG-PLGA NPs could have great potential as a targeted 5-FU delivery system for colon and breast cancer treatment.

KEYWORDS:

5-Fluorouracil; Cancer chemotherapy; FOL-PEG-PLGA conjugate; Haemocompatibility; Ligand-receptor mediated drug delivery; Nanoprecipitation.

PMID:
27825867
DOI:
10.1016/j.ijpharm.2016.11.012
[Indexed for MEDLINE]

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